酸血症和高钠血症可增强缺血后兴奋-收缩偶联的恢复。

Acidemia and hypernatremia enhance postischemic recovery of excitation-contraction coupling.

作者信息

Harada K, Franklin A, Johnson R G, Grossman W, Morgan J P

机构信息

Charles A. Dana Research Institute, Beth Israel Hospital, Boston, MA 02215.

出版信息

Circ Res. 1994 Jun;74(6):1197-209. doi: 10.1161/01.res.74.6.1197.

DOI:10.1161/01.res.74.6.1197

PMID:8187286

Abstract

The purpose of the present study was to determine whether Na(+)-H+ and Na(+)-Ca2+ exchanges modulate postischemic recovery of excitation-contraction coupling. Experiments were performed in 43 isolated isovolumic dog hearts perfused with blood (pH 7.40, 141 mmol/L Na+, 34 degrees C, paced at 2 Hz). A 3 x 3-mm region at the left ventricular (LV) apex was loaded with aequorin for monitoring [Ca2+]i simultaneously with LV pressure. No-flow ischemia for 2 to 3 minutes was followed by 20 minutes of aerobic reperfusion with (1) unmodified control blood (141 mmol/L Na+, pH 7.40), (2) acidemic blood (141 mmol/L Na+, pH 6.60, at 0 to 3 minutes of reperfusion), (3) hypernatremic blood (149 or 157 mmol/L Na+, pH 7.40, at 0 to 20 minutes of reperfusion), or (4) hyperosmotic blood (141 mmol/L Na+ + 30 mmol/L mannitol, pH 7.40, at 0 to 20 minutes of reperfusion). Reperfusion with unmodified control blood was immediately followed by an increase in [Ca2+]i and LV systolic and diastolic pressure that persisted for 2 to 3 minutes before returning to or below baseline. Ventricular arrhythmia occurred during this period (> 80%). This transient increase of [Ca2+]i was attenuated by acidemic or hypernatremic perfusate. With acidemic or hypernatremic reperfusion, recovery of LV developed pressure at 20 minutes was more complete than with unmodified control reperfusion: acidemic blood (n = 7), 93 +/- 3% (P < .01); hypernatremic blood (149 mmol/L Na+, n = 7), 89 +/- 2% (P < .02); hypernatremic blood (157 mmol/L Na+, n = 4), 91 +/- 2% (P < .01); and unmodified control blood (n = 17), 80 +/- 2%. With hyperosmotic reperfusion, recovery of LV developed pressure at 20 minutes was not improved (82 +/- 3%). From these results we conclude that (1) an increase in intracellular Ca2+ occurs transiently after no-flow ischemia and may cause arrhythmia and decreased Ca2+ responsiveness of the contractile elements, (2) acidemic and hypernatremic reperfusion ameliorates postischemic dysfunction by preventing the increase in intracellular Ca2+, suggesting that (3) Na(+)-H+ and Na(+)-Ca2+ exchange may play important modulatory roles during reperfusion.

摘要

本研究的目的是确定Na(+)-H+和Na(+)-Ca2+交换是否调节缺血后兴奋-收缩偶联的恢复。实验在43个离体等容犬心进行，用血液灌注（pH 7.40，141 mmol/L Na+，34℃，以2 Hz起搏）。在左心室（LV）心尖处一个3×3 mm的区域加载水母发光蛋白，用于与LV压力同时监测[Ca2+]i。进行2至3分钟的无血流缺血，随后进行20分钟的有氧再灌注，灌注液为：(1) 未修饰的对照血液（141 mmol/L Na+，pH 7.40）；(2) 酸血症血液（141 mmol/L Na+，pH 6.60，在再灌注的0至3分钟）；(3) 高钠血症血液（149或157 mmol/L Na+，pH 7.40，在再灌注的0至20分钟）；或(4) 高渗血液（141 mmol/L Na+ + 30 mmol/L甘露醇，pH 7.40，在再灌注的0至20分钟）。用未修饰的对照血液再灌注后，[Ca2+]i、LV收缩压和舒张压立即升高，并持续2至3分钟，然后恢复到基线或低于基线。在此期间发生室性心律失常（>80%）。这种[Ca2+]i的短暂升高被酸血症或高钠血症灌注液减弱。在酸血症或高钠血症再灌注时，20分钟时LV舒张末压的恢复比未修饰的对照再灌注更完全：酸血症血液（n = 7），93±3%（P <.01）；高钠血症血液（149 mmol/L Na+，n = 7），89±2%（P <.02）；高钠血症血液（157 mmol/L Na+，n = 4），91±2%（P <.01）；未修饰的对照血液（n = 17），80±2%。在高渗再灌注时，20分钟时LV舒张末压的恢复未得到改善（82±3%）。从这些结果我们得出结论：(1) 无血流缺血后细胞内Ca2+短暂升高，可能导致心律失常和收缩元件的Ca2+反应性降低；(2) 酸血症和高钠血症再灌注通过防止细胞内Ca2+升高改善缺血后功能障碍，提示(3) Na(+)-H+和Na(+)-Ca2+交换在再灌注期间可能起重要的调节作用。